Fine needle aspiration cytodiagnosis of liver tumors

OBJECTIVE: To present our experience with liver fine needle aspiration (FNA) diagnosis and the adjunctive use of cell blocks with reticulin stain. STUDY DESIGN: The authors reviewed the results of cytopathologic diagnosis obtained by FNA biopsy over a 1-year period, from January 2000 to December 2000, in patients who presented primarily with ultrasonographically suspected liver nodules. FNA smears from 936 patients and cell blocks from 796 patients were reviewed. RESULTS: Among the 936 aspirates studied, the most common malignancy was hepatocellular carcinoma (HCC), which was diagnosed in 427 cases (45.6%), followed by metastatic adenocarcinoma, with 52 cases (5.6%). The concurrent cell block was available in 796 cases. Among them, 574 (72.1%) contained sufficient tissue for diagnosis. Combining analysis of cytologic and histologic specimens, the sensitivity of ultrasound-guided FNA for diagnosis of liver tumors was 85.1% and the specificity 98.7%. The results were better than isolated cytologic analysis, which gave a sensitivity of 78.4% and specificity of 97.4%. The lower diagnostic accuracy of cytology resulted mainly from its lower ability to distinguish well-differentiated HCC from benign lesions. In the cell block sections with reticulin stain, all HCCs showed a decreased or absent reticulin pattern, whereas all the benign hepatocellular lesions usually had a normal trabecular reticulin framework. CONCLUSION: FNA cytology assisted by cell block examination can be an accurate and minimally invasive method for the definitive pathologic diagnosis of primary benign and malignant liver masses and for confirmation of tumors metastatic to the liver. In addition, reticulin staining should be part of the routine assessment of cell blocks. It enhances diagnostic accuracy, particularly for well-differentiated HCC.     

Beyond the suspicious thyroid fine needle aspirate. A review

Fine needle aspiration (FNA) is currently the best diagnostic tool for thyroid nodules. However, the cytologic category of indeterminate or suspicious lesion, which is found in 10-15% of cases, remains a challenge. Since neither clinical presentation nor intraoperative frozen section is often helpful in differentiating these lesions and since surgical procedures for benign and malignant lesions differ, there is a clear need to develop ancillary tests. In this review we identify 12 potential markers of thyroid malignancy that have been examined in thyroid cytologic samples. Although many of these markers hold promise as adjuncts to FNA cytology, multicenter studies have often shown limitations in the predictive value of these assays due to lack of specificity, sensitivity or both. The recent development, however, of tissue microarray techniques to validate promising new markers suggests that improvements in the approach to indeterminate thyroid FNA samples may soon be at hand. This review presents a summary of the issues facing the development of a clinically useful diagnostic test in the differential diagnosis of thyroid nodules.     

Pheochromocytoma. Cytologic findings on intraoperative scrape smears in five cases

BACKGROUND: There have been few studies describing the cytology of adrenal pheochromocytoma (PC). Although fine needle aspiration (FNA) for a preoperative diagnosis of PC is generally considered a contraindication, this tumor can be an unsuspected finding in adrenal FNA performed for other reasons. STUDY DESIGN: Scrape cytology smears prepared in five cases of PC were examined for different cytomorphologic features. The results were correlated with the corresponding permanent histologic sections. RESULTS: Previously described features, like cellular smears showing cells with abundant, poorly defined fragile cytoplasm, bare nuclei, anisonucleosis, "salt and pepper" chromatin, variable nucleoli and few ganglion cell-like cells, were noted. In addition, several previously unreported cytologic features were observed: (1) loosely cohesive PC cells along a ramifying, delicate central core; (2) intracytoplasmic microvesicular (not hyaline/homogeneous) globules; and (3) different arrangements of capillary-stroma and PC cells (Zellballen pattern; empty capillary rings; stroma with adherent, intact PC cells or fragments of disrupted PC cell cytoplasm). CONCLUSION: The cytologic appearance of PC may resemble that of other neuroendocrine tumors; however, it can be diagnostic when combined with proper clinical data and ancillary tests.     

Aspiration cytology, immunocytochemistry and electron microscopy of a malignant peripheral neuroectodermal tumor. A case report

The findings of fine needle aspiration (FNA) cytology, immunocytochemical staining and electron microscopy (EM) in a case of malignant peripheral neuroectodermal tumor (PNET) presenting as a soft tissue mass in the lateral abdominal wall are reported. The immediate evaluation of the aspirate revealed cells of a small round cell malignant tumor. To provide a specific preoperative diagnosis, additional cytologic material was aspirated for immunocytochemical and ultrastructural investigations. While the results of EM were nonspecific, allowing only the exclusion of other small round cell malignancies, immunocytochemical staining of the aspirate was suggestive of a PNET. The diagnosis of PNET was corroborated by histopathologic and immunohistochemical findings. This case indicates that an exact preoperative categorization of small round cell malignant tumors can be made by FNA biopsy in otherwise equivocal cases when immunocytochemical and ultrastructural techniques are also utilized.     

Fine needle aspiration diagnosis of osteitis fibrosa cystica (brown tumor of bone): a case report

BACKGROUND: Fine needle aspiration (FNA) cytologic diagnosis of bone lesions is controversial; opponents cite its low sensitivity and proponents emphasize its cost-effectiveness, specificity and rapid turnaround time. The focus of FNA cytology is most often to exclude malignancy, which may contribute to incomplete information sharing on the part of the health care team and the published low sensitivity of diagnostic cytology of osseous lesions. It is therefore incumbent upon cytopathologists to formulate a complete differential diagnosis of osseous lesions. CASE: A 72-year-old man, admitted for severe abdominal pain, underwent diagnostic computed tomography (CT) examination that incidentally revealed multiple abdominal and pelvic lytic bone lesions. CT-guided FNA of a lesion revealed bland histiocytic and spindled cells, prominent hemosiderin pigment and scattered multinucleated cells, findings consistent with osteitis fibrosa cystica. Subsequent consultation with the medical team revealed the patient's underlying secondary hyperparathyroidism. CONCLUSION: This case emphasizes the importance of correlating clinical history and radiologic findings to the accurate cytologic diagnosis of bone lesions. The benign cytomorphologic features of brown tumor should not be overlooked or be considered nondiagnostic in the hunt for suspected malignancy. FNA allowed confident exclusion of a malignant process and prevented unnecessary surgery and its inherent risks.     

Oral leiomyosarcoma in childhood. Report of a case with fine needle aspiration cytology

BACKGROUND: Leiomyosarcomas are rare tumors in the pediatric age group, and occurrence of this neoplasm in the oral cavity is exceedingly rare. This article highlights the fine needle aspiration (FNA) cytology diagnosis of a case of recurrent oral leiomyosarcoma in childhood. CASE: An 11-year-old male noticed a swelling in the oral cavity near the left lower jaw. It was excised and diagnosed as leiomyosarcoma on histopathology. Four months later the patient presented with a progressive swelling in the oral cavity that extended to the lower jaw. The recurrent swelling was subjected to FNA, and its cytologic features were consistent with leiomyosarcoma. There was a very good initial response to chemotherapy and radiation therapy. However, because of noncompliance with advice for further therapy, the patient had a second local recurrence and dissemination of the disease to the skeletal system, abdomen and thorax. FNA cytology diagnosis of the second locally recurrent lesion and abdominal mass were consistent with leiomyosarcoma. Immunocytochemical staining revealed a positive reaction in the cytoplasm of tumor cells for vimentin and desmin in the FNA smear and paraffin section, respectively. CONCLUSION: Fine needle aspiration cytology is a useful technique for detection of recurrence and metastasis during follow-up of childhood oral leiomyosarcoma.     

Use of a thin-layer technique in thyroid fine needle aspiration

OBJECTIVE: To investigate the efficacy of the ThinPrep Processor (Cytyc Corporation, Boxborough, Massachusetts, U.S.A) in fine needle aspiration (FNA) of thyroid gland lesions. STUDY DESIGN: This study included 459 thyroid FNA specimens obtained from patients who came to our endocrinology department with various thyroid disorders over 3 years. The cytologic material was prepared using both the conventional and ThinPrep method in the first 2 years (285 cases), while in the last one only the ThinPrep method was used (1 74 cases). The smears were stained using a modified Papanicolaou procedure and May-Grünwald-Giemsa stain. Immunocytochemistry was performed on thin-layer slides using specific monoclonal antibodies when needed. Thin-layer and direct smear diagnoses were compared with the final cytologic or histologic diagnoses, when available. RESULTS: Our cases included 279 adenomatoid nodules, 15 cases of Hashimoto thyroiditis, 45 follicular neoplasms, 14 Hürthle cell tumors, 58 papillary carcinomas and 1 5 anaplastic carcinomas. Thin-layer preparations showed a trend toward a lower proportion of inadequate specimens and a lower false negative rate. Cytomorphologic features showed some differences between the 2 methods. Colloid was less frequently observed on ThinPrep slides, while nuclear detail and micronucleoli were more easily detected with this technique. Moreover, ThinPrep appeared to be the appropriate method for the use of ancillary techniques in suspicious cases. CONCLUSION: Thin-layer cytology improves the diagnostic accuracy of thyroid FNA and offers the possibility of performing new techniques, such as immunocytochemistry, on the same sample in order to detect malignancy as well as the type and origin of thyroid gland neoplasms.     

Meningioma presenting as a parapharyngeal tumor: report of a case with fine needle aspiration cytology

BACKGROUND: Meningiomas rarely extend out of their intracranial confines through skull foramina to present as cervical tumors, where they would be accessible to fine needle aspiration (FNA) and thereby create difficulties in cytodiagnosis by mimicking other, more commonly aspirated head and neck tumors. CASE: A psammomatous meningioma arising intracranially and extending through the jugular foramen presented as a mass at the angle of the jaw clinically. On FNA cytology the diagnosis was suggested, but the cytomorphologic features overlapped with those of more commonly aspirated head and neck tumors, such as acinic cell carcinoma arising primarily in a salivary gland, metastatic papillary thyroid carcinoma and paraganglioma (glomus jugulare tumor). These possibilities had to be excluded through correlation with radiologic and intraoperative findings, which showed a dural-based tumor extending through the jugular foramen to assume a parapharyngeal location. Histology of the final excision specimen confirmed a psammomatous meningioma. CONCLUSION: The possibility of meningioma should be considered in the cytologic differential diagnosis of parapharyngeal tumors, particularly since its cytomorphologic features may mimic those of some of the more commonly encountered and aspirated head and neck tumors.     

Fine needle aspiration cytology of focal nodular hyperplasia of the liver

In five cases, the fine needle aspiration (FNA) cytologic study of ultrasonically detected solitary liver tumors yielded a diagnosis of focal nodular hyperplasia. Cytomorphologically, the lesions were characterized by the presence of both abundant normal hepatocytes and numerous epithelial cells in ductal formations, clusters or tightly packed groups in the FNA samples. In two of the five cases, the cytologic diagnosis was confirmed by subsequent histologic studies; in the remaining three cases, the clinical data were consistent with focal nodular hyperplasia of the liver. All five patients were women, four of whom had used oral contraceptives for long periods of time (5 to 15 years), which has previously been linked to the development of focal nodular hyperplasia of the liver. Based on the findings in this study, FNA cytology should be adequate for making the differential diagnosis of focal nodular hyperplasia versus liver-cell adenoma when solitary liver tumors are detected in such cases; it can yield a morphologic diagnosis and facilitate the decision as to whether surgical intervention is required.     

Fine needle aspiration cytology of malignant mesothelioma

The results of fine needle aspiration (FNA) cytology in 19 cases of malignant mesothelioma are presented. Adequate material for a diagnosis of malignancy was obtained in 17 cases, and in 8 cases a specific diagnosis of mesothelioma could be made. In four other cases, the findings were either consistent with or suggestive of mesothelioma; in four, accurate distinction from other neoplasms was not possible, and in two cases, adenocarcinoma was suggested. The spectrum of cytologic findings ranged from neoplasms of purely epithelial appearance through more pleomorphic biphasic neoplasms to anaplastic tumors. A combination of epithelial-like cell clusters, pavement-like sheets of epithelial cells with well-defined cell borders and prominent cell separation, dispersed angular cells with dense cytoplasm and some spindle-cell forms was the most specific cytologic pattern for mesothelioma. In four neoplasms, ultrastructural examination of aspirated material provided the additional evidence for a definitive diagnosis. The identification of hyaluronic acid within intracytoplasmic vacuoles, either in smears or in cell blocks, confirmed the diagnosis in three tumors. Only in one case, with a strong clinical background suggesting mesothelioma, was the cytologic preparation sufficient for diagnosis without ancillary diagnostic methods. FNA is of particular value in the diagnosis of pleural mesothelioma in patients who do not present with a pleural effusion. Obtaining material for cell block preparations, cytochemistry or ultrastructural study is generally necessary for definitive tumor typing.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Fine needle aspiration cytology diagnosis of a cutaneous granular cell tumor in a 7-year-old child. A case report

BACKGROUND: Granular cell tumors are neoplasms of uncertain histogenesis, although a neural origin is favored. Most reports on the cytologic features of granular cell tumors have been on lesions from the breast or respiratory tract. However, there are only a few reports on fine needle aspiration (FNA) cytologic diagnosis of cutaneous or soft tissue granular cell tumors. CASE: A 7-year-old girl presented with a skin lesion on her right forearm of one year's duration. The FNA smears showed sheets and clusters of oval to polygonal cells with an abundant amount of granular cytoplasm. Many single, scattered cells with similar morphology were seen in the background. Immunostaining for S-100 protein showed granular cytoplasmic positivity. The tumor was diagnosed as a benign granular cell tumor. The histopathology report on the excised lesion confirmed the FNA diagnosis. CONCLUSION: The cytopathologic features of granular cell tumors presenting as skin lesions are distinctive enough to allow a correct diagnosis on FNA cytology.     

Cytology and immunocytochemistry of bronchioloalveolar carcinoma

A study of the value of cytologic examination in the diagnosis of bronchioloalveolar carcinoma showed that fine needle aspiration (FNA) cytology is a definitive means of making the diagnosis of bronchioloalveolar carcinoma. In experienced hands, FNA cytology approached a diagnostic accuracy of 100%. With exfoliative cytology, technically adequate sputum samples offered an 82% diagnostic yield; sputum cytology should thus be considered as an adjunct method in establishing the diagnosis. Several cytologic features that strongly suggest the diagnosis of bronchioloalveolar carcinoma and help to differentiate it from adenocarcinomas of other body sites are outlined. It is also concluded that immunocytochemical stains have limited value in differentiating bronchioloalveolar carcinoma and other types of clear cell malignant neoplasms, including mesothelioma, unless a panel of antibodies is used, and are of no value in ascertaining whether the cells are benign or malignant.     

Spermatogenesis in azoospermic,formerly cryptorchid men. Use of needle aspiration techniques

OBJECTIVE: To assess the use of testicular needle aspiration techniques to evaluate fertility potential in azoospermic, formerly cryptorchid men. STUDY DESIGN: Fifteen consecutive adult azoospermic, formerly cryptorchid patients (eight unilateral and seven bilateral) were examined by needle aspiration techniques, fine (FNA) and large needle (LNAB) testicular aspiration biopsy, for cytologic and histologic analysis. Five of the 15 subsequently underwent surgical biopsy for attempted assisted fertilization. RESULTS: Spermatozoa or spermatids were detected by FNA cytology or LNAB histology in one or both testicles in 87.5% of the unilateral and 28.6% of the bilaterally affected, formerly cryptorchid patients (P = .041, Fisher's exact test). The addition of LNAB to FNA identified spermatids in one patient with unilateral cryptorchidism and only Sertoli cells on FNA cytology. Furthermore, LNAB differentiated testicles with the cytologic finding of only Sertoli cells into those with or without diffuse fibrosis. In the five patients in whom assisted fertilization was attempted, the needle aspiration techniques predicted the presence or absence of spermatozoa in the subsequent surgical biopsy. CONCLUSION: The two needle aspiration techniques can be used to assess the fertility potential of azoospermic, formerly cryptorchid men and to select patients for assisted fertilization.     

Diagnostic accuracy and role of immediate interpretation of fine needle aspiration biopsy specimens from various sites

A statistical analysis of the accuracy of the immediate interpretation of 425 fine needle aspiration (FNA) biopsies from various sites was performed. Preliminary interpretation of Diff-Quik-stained smears was rendered within a few minutes after performing the FNA biopsy, using diagnostic terminology similar to that of a surgical pathology report. The immediate assessment was documented in the formal cytology report and compared to the final diagnosis. For the entire series, the immediate interpretation had a sensitivity of 96%, a specificity of 97%, a positive predictive value (PV) of 98%, a negative PV of 95% and an efficiency of the test of 96%. There were 14 false-negative or falsely insufficient immediate interpretations and one false-positive immediate diagnosis. The diagnostic accuracy of the immediate interpretation of FNA biopsies from specific sites was also calculated; FNA biopsies of the pancreas were the least accurate procedure, having a sensitivity of 60% but a specificity of 100%. The role of the immediate interpretation of FNA biopsies is similar to the use of frozen sections in surgical pathology. An immediate assessment can (1) determine whether an adequate specimen is present, (2) render a specific preliminary diagnosis, (3) guide further clinical investigations or treatment, and (4) determine whether ancillary studies are needed to make a more accurate or specific diagnosis from the FNA specimen. Our results indicate that the immediate interpretation of FNA biopsies is an accurate procedure that should be routinely employed.     

Cytodiagnosis of bone tumors by fine needle aspiration

A retrospective study was undertaken of bone lesions examined by preoperative fine needle aspiration (FNA) cytology in our hospital during the ten-year period from 1970 to 1979. The 430 cytologically examined lesions were classified into three groups: inflammatory lesions, tumorlike lesions and tumors. A total of 54 patients had undergone surgery, with most of the lesions in those cases proven to be tumors or tumorlike by histologic study. Correlation between the histologic and FNA cytologic findings showed complete compatibility in 76% of the cases, partial compatibility in 13% and incompatibility in 11%. It is concluded that FNA biopsy is appropriate for identifying bone tumors and tumorlike lesions if sufficient numbers of tumor cells are obtained for morphologic examination. Although aspiration cytodiagnosis can be of considerable value in the recognition of certain bone lesions, it cannot replace formal tissue biopsy in the diagnosis of primary bone neoplasms. The morphology of several common bone tumors is described in detail and their differential diagnosis is discussed.     

Thyroid Cytology and Risk of Thyroid Cancer: Differences Among Indeterminate Specimens

ObjectiveTo assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies.MethodsWe attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available.ResultsOf the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%).ConclusionThe results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer. (Endocr Pract. 2004;10:330-334)     

Testicular germ cell tumors. Classification based on fine needle aspiration biopsy

Fine needle aspiration (FNA) biopsy was performed preoperatively on 13 patients with testicular germ cell tumors. The cytologic typing of the tumors was based on the presence or absence of seminoma, embryonal carcinoma, yolk-sac tumor, choriocarcinoma and teratoma in the aspirate. The cytologic findings showed good agreement with the histologic findings. Only four cases showed a single type of tumor; the other nine cases showed as many as four different tumor components. A few characteristic cytologic features proved to be sufficient for tumor typing; this suggests that FNA biopsy cytology can also be useful in identifying metastatic germ cell tumors in extra-gonadal sites.